PROJECT SUMMARY Positron emission tomography (PET) fused with X-ray computed tomography (CT) is a molecular imaging modality that uses radiolabeled tracers, for example 18F-fluorodeoxyglucose (FDG), to image biochemical processes in the living body. On the other hand, dual-energy CT (DECT) employs two different X-ray energies to obtain energy-differential attenuation information of tissue properties. DECT allows quantitative characterization of tissue composition by material basis decomposition that cannot be easily achieved by standard PET. Thus, DECT and PET may complement each other to enable a new multiparametric imaging solution. This complementarity has important implications in clinical diagnosis and therapy assessment. However, integration of DECT with PET would require either costly scanner hardware upgrade or significant modifications of imaging protocols to allow two X-ray CT scans, which is associated with increased radiation dose and scan cost. This project proposes a novel dual-energy CT imaging methodology that is enabled by the PET data in PET/CT instead of a second X-ray CT scan. The new method does not require any change of scanner hardware or add additional radiation dose or scan time except a standard time-of-flight PET/CT scan that is already available on most modern PET/CT scanners. We hypothesize that a quantitatively accurate 511 keV gamma-ray attenuation image can be obtained from time-of-flight PET emission scan data using advanced image reconstruction. The PET-enabled high energy gamma-ray ?CT? image is then combined with the X-ray (low-energy: ?140 keV) CT scan in PET/CT to produce a pair of dual-energy CT images. The goal of this proposal is to develop the feasibility of the proposed method and demonstrate its proof-of-concept use for imaging fat and calcification. We propose three specific aims to fulfill the goal in three years. Aim 1: To develop a statistically efficient image reconstruction method for PET-enabled gamma-ray CT. Aim 2: To measure the quantitative accuracy of PET-enabled gamma-ray CT using phantom studies with traditional PET transmission scan as the reference. Aim 3: To develop a PET-enabled dual-energy CT approach for quantitative analysis of material composition and validate it using phantom experiments. Successful completion of this project will establish the feasibility of a novel PET-enabled dual-energy CT (P-DECT) imaging method and make the method ready for starting a clinical imaging trial.